2, 3-dimercaptoquinoxaline derivatives



United States Patent 3,141,886 2,3-DMERCAPTQQUINOXALINE DERIVATIVES Klaus Sasse, Cologne-Stammheim, Richard Wegler, Leverkusen, and Giinter Unterstenhofer, Opladen, Germany, assignors to Farbenfabriken Bayer Aktiengesellschaft, Leverkusen, Germany, a gprporation of Germany No Drawing. Original application June 30, 1959, Ser.

No. 823,825, now ?atent No. 1963.

Ser. No. 244,026

11 Claims. (Cl. 260-250) The present invention relates to and has as its objects new and useful pesticidal compounds and processes for the production thereof. Generally the new compounds of this invention are derivatives of 2,3-dimercaptoquinoxalines which may be represented by the following general formula:

Ph l

in which A stands for one or two acyl' radicals or one CO, CS, CNR'- (R' being" alkyl or aryl),S- or SO-group, and Ph stands for an annelled benzene or naphthalene nucleus.

This application is a divisional application of copend ing application Serial No. 823,825, filed June 30, 1959, now US. Patent 3,091,613. p

According to D. C. Morrison and A. Furst (Journal of Organic Chemistry, vol. 21, page 470 (1956)), 2,3-dimercaptoquinoxaline may be obtained by reacting 2,3-dichloroquinoxaline with thiourea and subsequent alkaline splitting of the bis-thiouronium salt thus formed, or also by the action of phosphorus pentasulphide on 2,3-dihydroxyquinoxaline. pound may be alkylated with ethyl bromide in an alkalinealcoholic medium. Neither the free 2,3-dimercaptoquinoxaline nor its salts and alkylation products possess marked biocidal properties.

It has now been found that compounds having a very good acaricidal and ovicidal effect are obtainable by acylation of 2,3-dimercaptoquinoxaline or its substitution products. The term acylation is to'be understood in the widest possible sense comprising'inorganic as well as organic acyl derivatives. By reaction with 'rnonofunction'al acid halides or anhydrides products are obtained having one or two acyl radicals. Suitable acid halides'are for halides, sulphenic acid halides, sulphinic acid halides, sulphonic acid halides, chloroformic acid esters, thiocarboxylic acid ester halides, carbamic acid halides, chlorosulphonic acid esters or chlorosulphonic acid amides. In addition to acid halides or anhydrides, isocyanates or isothiocyanates' are likewise suitable for the production of acylation products of 2,3-dimercaptoquinoxalines, according to the invention.

By the reaction with bifunctional acid halides containing both halogen atoms at the same atom such as phosgene, thiophosgene, thionyl chloride or sulphuryl chloride, cyclic derivatives of 2,3-dimei'captoquinoxaline can be obtained in a surprisingly smooth reaction.

The production of the compounds according to the invention is carried out bygenerally known methods. Thus, acid halides which are not very sensitive to moisture such as aromatic carboxylic acid halides, chloroformic acid esters, sulphonic acid halides, may be reacted with 2,S-dimetcaptoquinoxaline or its nuclear substitution products in an aqueous medium or also in mixtures of water-miscible or -immiscible solvents in the 3,091,613, dated May. 28, Divided and this'application Dec. 12, 1962,"

It is further known that this com' 3,141,886 Patented July 21, 1964 ice presence of: acid-bidding agents such as alkali metal or alkaline earth .metal hydroxides or carbonates, tertiary amines and the like; Acid halides which are easily hydrolysed by water are expediently reacted with the salts, for example the alkali metal salts, of 2,3-d in' 1 erc2 1ptoquinoxaline or withthe free dimercaptoquinoxaline in nuclear substitution products is expediently carried out in an especially simple manner by treating 2, 3'-dicliloroquinoxaline or its derivatives with aqueous solutions of potassium or sodiuni sulphohydrate at an elevated temexample carboxylic acid halides, thiocarboxylic acid perature, in general below 100 C. This practical" proc ess, which gives quantitative yields, is likewise not yet known from literature.

The new compounds obtainable according to this process have an outstanding activity on various insects, es-

pecially spider mites, chiefly on living plants. Their. broad spectrum of activityisillfistratd'fof example by their suitability for combating Tetranychus telarius, Tetranychus althae'ae as well as Paratetranychus pilpsus." The chiefly very slight solubility of the compounds' and their high stability ensure a persistent effect. The majority have also a good ovicidal action so ihattre'ated plants can be? kept free of infestation for prolonged periods.

Theacaricidal action of some of the compounds according to the invention can be seen from the followin results which were ,obtained on, il trzinychu s telajrius with aqueodsconcentrations of 0.2%active ingredient'or lower after 4 8 hours. K

Under infection number after 8 days an Index is given which means '0-nd infection lvei y slight infection 2-m dium slight infection 3-medium infection 4heavy infection v,

5very heavy infection con? Morilnieocentratality tion Compound tion, afteri No.

perhours after 8 cent (perdays Contr 0 5 N s -c' o'o'o'rr 1 3 N SCOOOH N s-dooon,

a 0.2 0-1 N SCOOOHa on, v

| N s'ooooH3 o 0.2 100 0 & 2- 32 22 0 HgC- N s0ooo1r, N s-coodnn C 4 0.2 40 1 N S-COOCH5 acetone and" the The production of 2,3-dimercaptoquinoxaline and its' The tests have been carriedout' with 1 to 2 days oldeggs on pesticides in 'which'drip wet filter paper (with the above-said concentration) has been placed.

The aqueous solutions were prepared from mixtures of the active substance with equal partsof dimethylformamide and an emulsifier (commercially available aryl polyglycol ether) and subsequent dilution with water to the above-said concentration.

In addition to the liquid form, powdered mixtures with chalk, talc, bentonite and the like may also be employed for practical purposes. Also the application in the socalled slurry form'is sometimes advantageous, in this case emulsifiers have to be addedto the powdered formulation.

The following examples are'given'for the purpose of illustrating the inventionwithout limiting it thereto.

Example 1 30 parts of the disodium'salt of 2,3-dimercaptoquinoxaline are suspended in 250 parts of 'ben'zeneandti'eated' dropwise with stirring at'room temperature with 27.2 parts of chloroformic acid ethyl ester. The mixture is heated andboiled with stirring for 5 hours. The insoluble matter is filtered off hot, the filtrate evaporated down to dryness. 26 parts, i.e. 60% of the theoretical, of a compound having the formula which; after recrystallisation from diox'ane', shows melting.

point 170 C.

Example 3 In a similar manner to Example 2 there is obtained from parts of 6-chloro-2,3-dimercaptoquinoxaline and 14 parts of thiophosgene a product of the formula rated product is filtered off with suction,

6 in about 70% yield. Melting point 171-172 C. (after recrystallisation from glycohnonomethyl ether).

Example 4 Into a solution'of 19.4' parts of 2,3-dimercaptoquinoxaline and 12 parts of sodium hydroxide in 150 parts of water, gaseous phosgene" is introduced with ice-cooling at 5l0 C. until the solution shows an acid reaction. The excess p'hosgene is removed by blowing in air, the sepawashed andidried. After boiling the filter cake with dioxane, the yield is 8 parts (i.e. 33% of the theoretical) of a product having the formula Melting point 182-183 C. (dioxane).

There can be isolated from dioxane 8 parts The temperature rises to about- 50 C. The-mixture is stirred at this temperature for a further l 'hour, cooled" and pouredinto about 500 parts of water. The insoluble matter is filtered off with suction, washed'with water 'and dried. Yield: 8 parts (i.e. 65%' of the' theoretical) of a product which "chiefly consists 'of' a compound having the" formula N- s (g SO N s and melts at about 170* C. with decomposition.

Example 6 While stirring andcooling externaly with'ice and water there are introduced into 50 ml. of acetone below 15 C. at the same time (a) a solution of 30 grams of dimerc'aptoquinoxaline and 12.5 grains of sodium hydroxide in ml. of water, and- '(b) 'a-solution of'29.5 grams of chloroformic acid methyl ester in 100 'ml. of acetone. Stirring is continued for 1 hour and then 200 m1. of water are added; the crystals which separate are filtered with suction. There are obtained 35 grams (75% of the theoretical) of a product of the following formula:

N S0 0 o CH of the melting :point C. (alcohol).

ByJthe'same way but using instead of the chloroformic acid methyl ester a correspondingequinmolecular amount from chloroformic acid phenyl ester the corresponding di-' phenyl ester (III) of the melting point 80-82" C., which may be characterized by the following general formula:

Starting from phenyl-substituted, 2,3-dimercaptoquinoxaline there are obtained with different chloroformic acid esters according to the same method of preparation as said above the following compounds:

Melting Point, 0.

' N SGOOO2H5 A} 1 61. 63 N SCOOCzH /N\ /S C O O R H30 R=CH 91-93 (13 R=CzH 1 103-105 R=OI-IzCH Cl oily N S -C O O R 1 N S-OOOR 3 3O N S -C O O R N S-COOCzHs N SCOOCzH 1 From ligroin. 2 From alcohol.

Example 7 19.4 grams of 2,B-dimercaptoquinoxaline are dissolved by means of 8 grams of sodium hydroxide in 50 ml. of water and then further diluted with 150 ml. of acetone. While stirring and cooling below C. there are added slowly grams of thiocarbonic acid ethyl ester chloride. Stirring is continued for 1 further hour, the mixture is treated with 250 m1. of Water, and the crystals, which separate, are filtered with suction. 15 grams of the following compound are obtained:

Upon purifying the compound by dissolving it in hot benzene and precipitating by means of ligroin it melts at 136-138" C.

Example 8 23.8 grams of the disodium salt of 2,3-dimercaptoquinoxaline are mixed with 15 ml. of water. Thereafter 150 ml. of 'dioxane are added. At room temperature and by external cooling there are added dropwise 23.6 grams of dimethyl carbamic acid chloride. The mixture is then slowly heated to' 70 C. and kept for further 2 hours at this temperature. Upon cooling and adding 600 ml. of water the mixture is basified with sodium hydroxide at a pH of 11. The product which separates is filtered with suction and dried. There are obtained 10 grams of the following compound:

melting at 300 C. i 'Example 9 Into a mixture of 20 grams of 2,3-dimercaptoquinoxaline, 8 grams of sodium hydroxide, 30 ml. of water and ml. of acetone there are slowly introduced 24.7 grams of dimethyl thiocarbamic acid chloride. The temperature slowly rises to 50 C. and is kept at this temperature for a further half an hour. The mixture is cooled to room temperature and filtered with 600 ml. of water. After filtration with suction and drying there are obtained 25 grams (68% of the theoretical) of a compound of the formula N S(JN(CH;)2

N |N( a)z which may be recrystallized from dioxane, melting above 200 C. under decomposition.

Example 10 melting above 300 C. (from dioxane).

Example 11 A mixture of 30 grams of 2,3-dimercaptoquinoxaline,

12 grams of sodium hydroxide, 150 ml. of acetone and 150 ml. of water is cooled, and while stirring there are introduced dropwise 43.4 grams of benzoyl chloride. Stirring is continued for 5 hours, whereby further sodium hydroxide solution is introduced slowly to keep the pH value at about 12-13. At the end the mixture has to be practically neutral. The precipitate is filtered with suction and treated with boiling alcohol. Upon filtration from the alcohol there. are obtained 18 grams of a monobenzoyl compound of the following formula:

melting above 300 C.

Example 12 Into a suspension of 23.8 grams of the disodium salt of 2,3-dimercaptoquinoxaline in 150ml. of dioxane and 15 ml. of water there are-introduced while stirring and cooling to room temperature 40.9 grams of perchloro methyl mercaptaneu Stirring iscontinued for half an hour at 35-40 C. After cooling water is added and the precipitated product is filtered with suction and dried. Yield: 24 grams (50% of" the theoretical) of the following compound N s-scon melting at 132-134 C. (from ethyl acetate) Example 13 Into a solution of 31.2 grams of 6-methyl-2,3'-dimer' captoquinoxaline and 14 grams of sodium hydroX-idein 200 ml. of water there are added-slowly below 15 C. 19 grams of thiophosgene. Stirring is continued for 30 minutes at roomtemperature, then the-product is filtered with suction and dried. Yield: 29.8 grams (80% of the theoretical) of the following compound CHsO- having a melting point of 162-164 C. (from dioxane). In an. analogous manner there are obtained from other benzene-substituted 2,3-dimercaptoquinoxalines the following compounds:

( 3) zN-Sa- 202 (from butano N S (g C=S 225-230 (from butauol).

OH; I

([1 0:8 138-140 (from I carbontetrachloride] N S llgroin).

Melting Point, o 0.

OH; I

l N s- A} 0:8 167 (from ben- Z8116 HBO N s. H3O 0=s agar- 30m oxane v\ Example 141 350grams-of 61-methyl-2Q3edimercaptoquinoxaline and 1'35 grams of sodium hydroxide are dissolvedr'in 200fmll of water. While stirring andcooling there is introduced atvastemperature below 15 C. gaseousrphosgene. While constantly adding dropwise a 25% sodium hydroxide. solution the pH value is kept at 1343.2. The introducing of phosgene is interrupted w-henadding340 grams of sodium hydroxide (in the form of'its 25% solution). The suspension is filtered with suction and the filter cake is washed neutral with water and dried. Yield: 270

} grams (69% ofth'e theoretical) ofthe following dithiocarbonate Melting point, CI

N St

By the same way there are obtained the. following compounds:

171=172 (from toluene).

Melting point, C.

(from ligroin).

175-180 (from ligroin).

208 (from toluene).

-166 (from dioxane).

172-176 (from butanoU- ligroin) Melting point, C.

' N S (GHa)aNSOz o=o 182. /C\ N/ S 01 N S i 4} :0 250 (xylene).

Example 15 16.5 grams of 5-carboxy-2,3-dimercaptoquinoxaline are dissolved in 100 ml. of water by means of 6 grams of sodium hydroxide. Below 15 C. there is introduced a stream of gaseous phosgene. A solution of 12 grams of sodium hydroxide (in 50 ml. of water) is added dropwise to keep the pH value at 13l3.2. After the sodium hydroxide solution has been added introduction of phosgene is continued until the solution reacts neutral. The product obtained is filtered with suction, washed neutral with water and dried. There are obtained 11 grams of the following compound melting above 300 C. (from dioxane).

The 2,3-dimercaptoquinoxaline-5-sulfonamide yields by' the same way the following compound melting at 225-230 C.

Example 16 18 grams of finely divided disodium salt of 2,3-di-' mercaptoquinoxaline are suspended in 100 ml. of dioxane.

At room temperature there are added dropwise' 13.2'

grams of phenylisocyane dichloride. Stirring is continued for 1 hour at room temperature and then for 2 further hours at 80 C. The mixture is cooled to room temperature and is then poured into 750 ml. of water. The crystals which separate are filtered with suction, washed with water and dried. 14 grams of the following compound are obtained The precipitated crystals are filtered with suction, washed and dried. There are obtained 15 grams of the following compound:

C melting above 290 C.

12 What is claimed is:

1. A compound of the formula R N SX R N/\SY wherein R and R each stand for a member selected from the group consisting of hydrogen, lower alkyl, halogen, nitro, lower alkoxy, aminocarbonyl, aminosulfonyl and carboxyl; X stands for a member selected from the group consisting of hydrogen, lower alkoxycarbonyl, phenyloxycarbonyl, lower alkoxy-thiocarbonyl, aminocarbonyl, aminothiocarbonyl, phenylcarbonyl and trichlorornethylsulfenyl; Y is a member selected from the group consisting of lower alkoxycarbonyl, phenyloxycarbonyl, lower alkoxy-thiocarbonyl, aminocarbonyl, aminothiocarbonyl, phenylcarbonyl and trichloromethylsulfenyl.

2. A compound of claim 1 wherein R and R are each hydrogen and X and Y are each lower alkoxycarbonyl.

3. A compound of claim 1 wherein R and R are each lower alkyl and X and Y are each lower alkoxycarbonyl.

4. A compound of claim 1 wherein R and R are each hydrogen and X and Y are each phenyloxycarbonyl.

5. A compound of claim 1 wherein R and R are each hydrogen and X and Y are each lower alkoxy-thiocarbonyl.

6. A compound of claim 1 wherein R and R are each lower alkyl and X and Y are each phenoxycarbonyl.

A compound of the following formula:

N S-COOOH;

8. A compound of the following formula:

9. A compound of the following formula:

N S-SC C13 10. A compound of the following formula:

I N s-0ooons N s-oooorr 11. A compound of the following formula:

s-COOCgH5 No references cited. 

1. A COMPOUND OF THE FORMULA 